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PubMed1999

[Health council report: "Antimicrobial growth promoters"].

The Health Council of the Netherlands has issued a report on the risk of development of resistance among bacteria as result of the use of antibiotics as growth promotors in livestock farming. The committee appointed by the Health Council conclude that the use of antimicrobial growth promotors contributes to the problem of resistance among human pathogens. The conclusions are based on evidence regarding the development of resistance in livestock as the result of the use of antimicrobial growth promotors, the possibility of colonisation/infection of humans with resistant bacteria from the intestinal flora of productive livestock, and the transfer of resistance genes from livestock bacteria to human pathogenic microorganisms. Effective measures for the limitation of the public health risk should focus on termination of the use of antimicrobial growth promotors that confer resistance to (related) antibiotics currently used (or which will be available) to treat patients suffering from bacterial infections. In addition, the committee advised ending the use of antimicrobial growth promotors in 3 years.

Animals↗
PubMed1989

Suppression of the oropharyngeal and gastrointestinal microflora by ciprofloxacin: microbiological and clinical consequences.

The impact of ciprofloxacin on the human oropharyngeal and gastrointestinal microflora has been studied by several authors during the last years. The use of ciprofloxacin for selective decontamination in immunocompromised patients has also been investigated. This review article summarizes the published data concerning these studies. The results show that the impact on the oropharyngeal microflora is minor. Administration of ciprofloxacin leads to a rapid elimination of the major components of the aerobic Gram-negative intestinal microflora. The aerobic Gram-positive flora is partly affected, while the impact on the anaerobic microorganism is minor. Oral ciprofloxacin given prophylactically to immunocompromised patients during severe granulocytopenia prevented colonization with potentially pathogenic aerobic Gram-negative rods, and reduced the incidence of infections caused by these microorganisms. There was no effect on the incidence of aerobic Gram-positive or fungal infections. Administration of ciprofloxacin seems not to predispose to the development of resistant microorganisms.

Bacteria↗
PubMed1984

[Pharmacotherapy of acute infant enteritis].

The management of acute diarrhea in infants with drugs is justified only where these drugs have specific interactions with the pathophysiologic mechanisms involved. Most of the infectious diarrheas are self-limited, many patients recover spontaneously. Antimicrobial drugs are only indicated if mucosal destruction takes place and symptoms of dysentery respectively inflammation are observed. Some authors propose to treat newborn and young infants in case of doubt. If antimicrobial drugs are given uncritically a selection of not obligatory microorganisms can occur, or the number of asymptomatic carriers increases. There is no confirmation that drugs like adsorbents (kaolin, pectin, charcoal) or lyophilized microorganisms have a therapeutic effect. In contrast morphine derivatives like loperamide act not only by slowing the intestinal motility but also by inhibiting the secretion mechanisms of the enterocyts. Nevertheless these drugs can not be recommended for infants since ileus symptoms have been observed.

Anti-Bacterial Agents↗
PubMed2000

Effect of supplements with lactic acid bacteria and oligofructose on the intestinal microflora during administration of cefpodoxime proxetil.

Thirty healthy volunteers in three groups participated in a study of the effect on the intestinal microflora of oral supplementation with Bifidobacterium longum, Lactobacillus acidophilus and oligofructose, an indigestible oligosaccharide, during oral administration of cefpodoxime proxetil bd for 7 days. Those in group A also received an oral supplement with c.1011 cfu of B. longum BB 536 and L. acidophilus NCFB 1748 and 15 g oligofructose daily, those in group B received a supplement with oligofructose only and those in group C received placebo, for 21 days. In all three groups there was a marked decrease in aerobic microorganisms, involving mainly a rapid and almost complete disappearance of Escherichia coli (P: < 0.05) during antimicrobial administration and, thereafter, an overgrowth of enterococci (P: < 0.05). The number of intestinal yeasts also increased significantly (P: < 0.05) in groups A and B over the same period. There was a dramatic decrease in anaerobic microorganisms on day 4 of administration, mainly caused by loss of bifidobacteria (P: < 0.05) in all groups. The number of lactobacilli also decreased but was significantly higher in group A than in group C at the end of cefpodoxime proxetil administration. Clostridium difficile was found in only one person from group A, but six persons each in groups B and C. Of the bifidobacterial strains isolated from the faecal samples in group A, one was similar to the strain of B. longum administered, but most volunteers were colonized by several different strains of B. longum during the investigation period. The administered strain of L. acidophilus was recovered from six patients in group A.

Adult↗
PubMedDate not supplied

[Effect of enteroviruses on the ecology of intestinal bacteria].

The rate of isolation of some enteric bacteria from normal children and those suffering from diseases caused by ECHO viruses was studied. Enterovirus infection was shown to cause characteristic disturbance of microbial biocenosis in the large intestine differing from similar disorders in other intestinal diseases: a decrease in the total number of enterobacteria with predominant replication of escherichia not fermenting lactose. Enteroviruses exert a mediated effect on enteric microorganism population changing the physico-chemical properties of their environment.

Child, Preschool↗
PubMedDate not supplied

Gastrointestinal surface protection and mucosa reconditioning.

BACKGROUND: There is increasing evidence that preservation of the ecology of the gastrointestinal tract and the surface protection system--surfactants, mucus, and fiber--is important for the outcome in postoperative trauma patients, patients after bone marrow and liver transplantation, and patients with HIV or AIDS. Approximately 50% of the nourishment of the small intestine and > 80% of the nourishment of the large intestine comes from the lumen. This is especially deleterious to the large intestine. Within less than a week of intestinal starvation--even in the presence of intense parenteral nutrition--a mucosal atrophy is observed, promoting translocation of potentially pathogenic microorganisms. Enteral nutrition is crucial to the outcome in many of these conditions. If however, such a nutrition is based on simple carbohydrates, peptides, amino acids, or fatty acids, most of the nutrition administered will be absorbed in the upper gastrointestinal tract. Complex fibers and proteins can be regarded as nutrients especially destined to the lower gastrointestinal tract. They are fermented by the probiotic flora, normally colonizing the colonic mucosa, and the necessary nutrients: short-chain fatty acids and amino acids such as arginine and glutamine are produced at the level of the colonic mucosa. Careless antibiotic treatment reduces or eliminates this flora, induces local mucosal starvation, and makes the patients vulnerable to opportunistic infections and microbial intestinal translocation. METHODS AND RESULTS: In this review the role of the different ingredients of the surface protection system are discussed. A program to recondition the intestines, particularly the colonic mucosa by resupply of species-specific lactobacilli, surfactants, amino acids (especially glutamine), and oat fiber (beta-glucans) is suggested. Extensive experience in animal models and early experience in a patient population are summarized and discussed. Oat has been chosen as a substrate for fermentation because it contains 100 times more of membrane lipids (surfactants) than any other food, has a favorable amino acid pattern (rich in glutamine), and is rich in water-soluble, fermentable-fiber beta-glucans. More than 1000 isolates of human-specific lactobacilli have been studied. Some strains, especially those of plantarum type, have proven effective in colonizing the colonic mucosa, suppressing the potentially pathogenetic flora, and may have other probiotic effects as well. CONCLUSION: A totally new enteral formula has been designed based on probiotic bacteria and fiber and aimed at colonizing the intestinal mucosa with a local probiotic effect and fermentation of fiber.

Animals↗
PubMed2003

High cell density cultivation of probiotics and lactic acid production.

The commercial interest in functional foods that contain live microorganisms, also named probiotics, is paralleled by the increasing scientific attention to their functionality in the digestive tract. This is especially true of yogurts that contain strains of lactic-acid bacteria of intestinal origin, among these, Lactobacillus delbrueckii ssp. bulgaricus is extensively used in the dairy industry and it has been demonstrated to be a probiotic strain. In this work we describe high cell density cultivations of this microorganism also focusing on the stereospecific production of lactic acid. Key parameters such as medium composition (bactocasitone concentration) and diverse aeration conditions were explored. The results showed that the final concentration of biomass in anaerobic fermentation was lower than the one obtained in microaerophilic conditions, while it gave a very high productivity of lactic acid which was present as a racemic mixture in the permeate. Fermentation experiments carried out with air sparging, even at very low flow-rate, led to the production of the sole L(+) lactic acid giving sevenfold increase in biomass yield in respect to the batch cultivation. Finally, a mathematical model was developed to describe the microfiltration bioprocess applied in this research considering an inhibition kinetic and enucleating a suitable mathematical description for the decrease of the transmembrane flux.

Bioreactors↗
PubMed1977

[Necrotic enteritis in broiler chickens. III. Study of the factors favoring the multiplication of Clostridium perfringens and the experimental transmission of the disease].

Necrotic enteritis was reproduced experimentally in two week old broiler chickens by intravenous injection and also by oral administration of a pure culture of Clostridium perfringens. In the first experiment, gross and microscopic intestinal lesions, typical of necrotic enteritis, were observed in all diseased birds and mortality was obtained only in the group of birds that were injected with 0.4 ml or more of the pure culture of the microorganism. In the second experiment, the highest mortality was noted in the group of birds that received orally, in addition to the Clostridium culture, a solution of sodium bicarbonate, to obtain an alkaline intestinal content and opium to decrease the intestinal peristaltism. The gross and microscopie intestinal lesions of the diseased and killed birds were more severe than those observed in the other groups and were similar to those encountered in field outbreaks of necrotic enteritis.

Animals↗
PubMed1994

Mycobacterium paratuberculosis in intestinal tissue from patients with Crohn's disease demonstrated by a nested primer polymerase chain reaction.

BACKGROUND: The etiology of Crohn's disease remains unknown, but current research has concentrated on autoimmunity and/or mycobacterial infection. The polymerase chain reaction (PCR) enables the detection of genetic material even when very few microorganisms are present. METHODS: A nested primer PCR for detection of a multi-copy insertional element (IS900) specific for Mycobacterium paratuberculosis was applied to DNA extracted from fresh and from paraffin-embedded intestinal tissue obtained from patients undergoing surgery. RESULTS: In fresh intestinal tissue from 11 of 24 patients with Crohn's disease, from 2 of 10 patients with ulcerative colitis, and from 3 of 28 patients with other colonic disorders, specific M. paratuberculosis DNA was found. In paraffin-embedded Crohn's disease tissue the presence of specific M. paratuberculosis DNA was also increased. CONCLUSIONS: Whether the presence of M. paratuberculosis is connected to the inflammatory bowel disease or is a mere coincidence cannot be stated. We find this presence interesting and encouraging for further investigations.

Adolescent↗
PubMed2005

Prevention of infections by probiotics.

'Viable bacteria that exhibit beneficial effects for health based on improvement of balance of intestinal bacterial flora' was the most common definition of probiotics, but the diversity of their action mechanisms, including immune regulation, has been clarified, and probiotics have recently been broadly defined as 'live microorganisms which when administered in adequet amounts confer a health benefit on the host'. Coined words such as prebiotics, describing non-digestible food fiber components that contribute to host health by activating proliferation and function of beneficial intestinal bacteria, and synbiotics, describing a combination of probiotics and prebiotics have also been established as medical expressions. In this report, clinical studies of probiotics, prebiotics, and synbiotics on prevention of infection by various infectious diseases in humans are reviewed. The effects of and action mechanisms against sporadic intestinal infectious diseases that are difficult to investigate in humans (enterohemorrhagic Escherichia coli and Salmonellosis) in experimental animal models are also reviewed. Finally, points necessary for clarification of the role of probiotics in health care, and their functions in health care foods are discussed.

Animals↗
PubMed2001

Bifidobacteria: genetic modification and the study of their role in the colon.

Bifidobacteria are among the most common bacteria in the human intestine and are thought to have a positive effect on human health. Therefore, there is an increasing interest in using these microorganisms as probiotics, either in fermented dairy products or formulated as tablets. However, convincing scientific data supporting their health claims are scarce. The study of the role of bifidobacteria in the colon is complicated by the fact that they are part of a complex ecosystem also interacting with the human host and by the fact that their in vivo study encounters many ethical constraints. Several tools have been developed at TNO with which the role of bifidobacteria can be studied. These include (i) an efficient transformation protocol for the introduction of foreign DNA into Bifidobacterium strains and (ii) in vitro models of the stomach/small intestine (TIM-1) and large intestine (TIM-2), creating an environment closely resembling that of the in vivo situation. With these tools, biomarkers from bifidobacteria quantifying their positive effect on gut health can be identified.

Bifidobacterium↗
PubMedDate not supplied

[Absorption, distribution and excretion of vitamin B12].

During our first communication [1], the complexity of vitamin B12 digestive transport was considered. This second presentation demonstrates the route of the vitamin in the body. As cobalamin or vitamin B12 has existed for four billion years, they figure without any doubt amongst those molecules which have the most complex structure. The rarity of an architecture organised around a cobalt atom confirms their high level of originality. Their exceptional character is reflected in their cycle such as for mammals and for man where the intervention of binders, such as intrinsic factor, transcobalamin and haptocorrin is necessary for transporting them. As far as cellular metabolism is concerned, it is especially loaded sometimes with folates in the transfer of the methyl group. The molecules are spiked with hydrophobic sites. Their membrane transfer is facilitated by several types of receptors. The intestinal absorption, which appears to require the presence of two receptors and two transporters, remains for the moment a unique assimilation model. The very probable existence of an enterohepatic cycle as well as a renal reabsorption saves this molecule, itself synthesised by microorganisms only.

Adult↗
PubMed2005

Microencapsulated subunit vaccine approach to enterotoxigenic Escherichia coli and other mucosal pathogens.

Infections of the intestinal, urogenital, and respiratory tracts are serious health problems worldwide from both a morbidity and mortality perspective. Mucosal pathogens attach to surfaces of mucosa as a prerequisite for colonization and subsequent pathogenesis. By expressing various surface adhesins (colonization factors, CF) they are able to bind to specific mucosal receptors. Enterotoxigenic Escherichia coli (ETEC) can express numerous CF that allow them to attach to a variety of hosts. Mucosal immunity directed against pathogenic microorganisms is critical in host protection with secretory IgA being particularly important in preventing microoganisms from colonizing host cells. M cells likewise have an important immunological function in the small intestines by binding and transporting antigens to lymphocytes and macrophages thus enhancing the immune response. The use of subunit vaccines, such as antigen encapsulated microspheres, can act to effectively deliver specific antigens so as to optimize their immunological response. With the threat of bioterrorism becoming a reality in recent years, the miroencapsulation of antigens from potential bioterrorist agents may be an effective method of delivery so as to induce a level of protection in at risk individuals. The encapsulation of ETEC colonization factors in microspheres and their subsequent administration in small animals and humans has been conducted for many years. Evidence suggests that this type of delivery system for ETEC antigens may enhance their immunogenicity and provide protection against this microorganism.

Adhesins, Escherichia coli↗
PubMed2001

Effect of antimicrobial agents on the ecological balance of human microflora.

The normal microflora acts as a barrier against colonisation of potentially pathogenic microorganisms and against overgrowth of already present opportunistic microorganisms. Control of growth of opportunistic microorganisms is termed colonisation resistance. Administration of antimicrobial agents, therapeutically or as prophylaxis, causes disturbances in the ecological balance between the host and the normal microflora. Most studies on the impact of antimicrobial agents on normal microflora have been carried out on the intestinal flora. Less is known on the effects on oropharyngeal, skin, and vaginal microflora. Disturbances in the microflora depend on the properties of the agents as well as of the absorption, route of elimination, and possible enzymatic inactivation and/or binding to faecal material of the agents. The clinically most common disturbances in the intestinal microflora are diarrhoea and fungal infections that usually cease after the end of treatment. A well-balanced microflora prevents establishment of resistant microbial strains. By using antimicrobial agents that do not disturb colonisation resistance, the risk of emergence and spread of resistant strains between patients and dissemination of resistant determinants between microorganisms is reduced. In this article, the potential ecological effects of administration of antimicrobial agents on the intestinal, oropharyngeal, and vaginal microflora are summarised. The review is based on clinical studies published during the past 10 years.

Anti-Bacterial Agents↗
PubMed1996

NTP Comparative Toxicity and Carcinogenicity Studies of o-Nitrotoluene and o-Toluidine Hydrochloride (CAS Nos. 88-72-2 and 636-21-5) Administered in Feed to Male F344/N Rats.

o-Nitrotoluene and o-toluidine hydrochloride are structurally related chemicals that are suspected and demonstrated animal carcinogens, respectively. The metabolic potential of the gastrointestinal flora is considered an important factor in o-nitrotoluene-induced toxicity and involves the reduction of the nitro group to the corresponding amine (forming o-toluidine). These studies were designed to 1) compare the target organ toxicities of o-nitrotoluene and o-toluidine hydrochloride administered in feed at approximately equimolar doses (5,000 ppm) to male F344/N rats for 13 or 26 weeks, 2) determine the potential progression or reversibility of toxic or proliferative lesions following chemical withdrawal (stop-exposure) for 13 weeks after 13 weeks of exposure, and 3) examine the effect of antibiotic-altered gastrointestinal flora on the toxicity and/or carcinogenicity of o-nitrotoluene. o-Nitrotoluene and o-toluidine hydrochloride caused mesothelial hyperplasia and mesothelioma in male rats after 13 or 26 weeks of dietary exposure. The incidence of mesothelioma was greater and the latency was less in rats administered o-nitrotoluene than in rats administered o-toluidine hydrochloride. Additionally, o-nitrotoluene caused testicular degeneration in rats. Effects of o-nitrotoluene administration in the liver included progressive, irreversible increases in liver weight and irreversible increases in the incidences of cytoplasmic vacuolization and oval-cell hyperplasia. Placental glutathione S-transferase (PGST)-positive foci of cellular alteration occurred in the liver after 13 weeks of o-nitrotoluene exposure, and the number and size (as reflected by the volume fraction) of foci were increased after 26 weeks of continuous exposure. During the recovery period, the number of PGST-positive foci in rats in the stop-exposure group decreased slightly, but the size of the foci continued to increase. After 26 weeks, cholangiocarcinoma occurred in 2 of 20 rats in the stop-exposure group and 1 of 20 rats in the continuous-exposure group administered o-nitrotoluene. In contrast, liver effects in rats administered o-toluidine hydrochloride consisted of minimal hemosiderin accumulation in Kupffer cells; the incidence of this lesion in the stop-exposure group decreased during the recovery period. o-Toluidine hydrochloride caused fewer and much smaller PGST-positive foci than those caused by o-nitrotoluene. o-Nitrotoluene caused an accumulation of hyaline droplets in the renal tubule epithelium; this accumulation did not increase in severity with continued exposure and completely regressed during the recovery period. Exposure to o-toluidine hydrochloride did not cause hyaline droplet accumulation but did cause an accumulation of hemosiderin pigment in renal tubule epithelium. This change progressed in severity during the 26-week continuous-exposure study but decreased in severity in the stop-exposure study during the recovery period. Exposure to o-nitrotoluene or o-toluidine hydrochloride caused increased incidences of hematopoiesis, hemosiderin accumulation, and capsular fibrosis in the spleen. In rats administered o-toluidine, spleen effects were much more prominent and were also reflected by congestion and markedly increased spleen weights. During the recovery period for the stop-exposure groups administered either compound, incidences of hemosiderin accumulation and hematopoiesis were decreased, but the capsular fibrosis did not resolve. Hyperplasia of the transitional epithelium in the urinary bladder was observed only in rats administered o-toluidine hydrochloride; this lesion did not increase in severity after 26 weeks of continuous exposure and completely regressed in the stop-exposure group during the recovery period. Alteration of the gastrointestinal flora by daily gavage administration of antibiotics did not affect the pattern or severity of toxicity at any site or the development of mesothelioma in rats exposed to o-nitrotoluene, although cholangiocarcinomas that occurred in three rats with the normal flora did not occur in groups with the altered intestinal flora. Subsequent studies determined that the antibiotic regimen used was effective only in reducing the gut population of aerobic microorganisms and had little effect on obligate anaerobes, which are thought to play a mayor role in nitro group reduction. In summary, these studies confirmed the target organs and compared the relative toxicity for o-nitrotoluene and o-toluidine hydrochloride administered to male F344/N rats at equimolar concentrations in feed. With the exception of the spleen toxicity observed with each chemical, but more prominently with o-toluidine hydrochloride, morphologic effects of exposure to each of these chemicals in the testis/epididymis, liver, kidney, and urinary bladder were different. The results of these studies demonstrate the somewhat greater relative carcinogenic potential of o-nitrotoluene compared to o-toluidine hydrochloride after 13 or 26 weeks of administration based on the occurrence of mesothelioma and cholangiocarcinoma. The apparently lower potency of o-toluidine hydrochloride relative to o-o-nitrotoluene in the induction of mesothelioma suggests that simple intestinal reduction of the nitro group may not be sufficient for carcinogenic activity in the mesothelium.

Journal Article↗
PubMed1984

[Intestinal microflora of monkeys, normal and in pathology, and its correction by preparations of live bacteria from human biocenosis (coli bacteria, bifikol and bifidum bacterin)].

The study of the qualitative and quantitative composition of intestinal microflora in 15 anthropoid apes, 60 lower primates and 72 monkeys with clinically pronounced dysbacteriosis was made, which revealed the prevalence of microorganisms belonging to the genus Proteus, a decrease in the biological activity of normal Escherichia coli and in the content of bifido- and lactobacteria. The treatment of 39 rhesus and pig-tailed macaques with the preparations of live bacteria occurring in normal human microflora led to clinical convalescence and the normalization of the bacteriocenosis, while in 33 control animals no positive shifts in clinical and bacteriological data were observed. The essential similarity of the composition of intestinal microflora in higher and lower primates and in man makes it possible to use these animals as models for testing the effectiveness of new biological preparations and determines the expediency of using bacterial therapy for the treatment of monkeys at the period of acclimatization.

Animals↗
PubMed1978

The mucosa-associated microflora of the rat intestine: a study of normal distribution and magnesium sulphate induced diarrhoea.

Specimens of intestinal mucosa of rats were examined closely to determine the distribution of the mucosa-associated microbial flora. Six distinct zones were found along the length of the intestinal tract. The first zone, in the small intestine 50 cm or more from the ileocaecal junction, had no associated flora: however, each of the five other zones had different populations of microorganisms associated with the mucosa. Some of these organisms have not been reposted previously. Treatment of rats with oral doses of the purgative magnesium sulphate resulted in dramatic changes in the distribution of these mucosa-associated microorganisms. The normal flora of ileal and caecal crypts disappeared, while the organisms in colonic crypts were unchanged. Large numbers of mucosa-associated bacteria appeared in the stools of treated animals.

Animals↗
PubMed1991

New model for analysis of mucosal immunity: intestinal secretion of specific monoclonal immunoglobulin A from hybridoma tumors protects against Vibrio cholerae infection.

Secretory immunoglobulin A (sIgA) plays a role in defense against Vibrio cholerae and other microorganisms that infect mucosal surfaces, but it is not established whether sIgA alone can prevent disease. We report here a strategy for identifying the antigen specificities of monoclonal sIgA antibodies that are capable of providing such protection. IgA hybridomas were generated from Peyer's patch lymphocytes after oral immunization with V. cholerae Ogawa 395. A clone was selected that produced dimeric monoclonal IgA antibodies directed against an Ogawa-specific lipopolysaccharide carbohydrate antigen exposed on the bacterial surface. Hybridoma cells were used to produce subcutaneous "backpack" tumors in syngeneic mice, resulting in secretion of monoclonal sIgA onto mucosal surfaces. Neonatal mice bearing anti-lipopolysaccharide hybridoma backpack tumors were specifically protected against oral challenge with 100 50% lethal doses of virulent Ogawa 395 organisms. Thus, the IgA hybridoma backpack tumor method identifies protective epitopes in the mucosal system and demonstrates that a single monoclonal sIgA can be sufficient to protect against intestinal disease.

Animals↗